The Hepatitis B virus core (HBc) protein has a somewhat unique structure comprised of two anti-parallel α-helices which form a characteristic “spike” structure. Two HBc molecules then spontaneously dimerise to form a twin spike bundle. This bundle is the building block of a virus like particle (VLP). VLPs are attractive vaccine systems since their highly repetitious sequence delivers multiple copies of the antigen. Furthermore, the lack of viral nucleic acid makes them a particularly safe vector. HBc is particularly interesting as a vaccine carrier since it has several sites into which antigenic sequences may be inserted. The extreme immunogenicity of HBc is then also imparted to the inserted sequence, thus making that too immunogenic. The optimal insertion site is the Major Insertion Region (MIR). However, it was shown previously that when a large or hydrophobic sequence is inserted into the MIR, then monomeric HBc fails to dimerise and a VLP does not form. This resulted in a massive loss of immunogenicity.
Currently there is no licensed vaccine available for the bacterial biothreat agents Burkholderia pseudomallei and Burkholderia mallei, the causative agents of melioidosis and glanders respectively.